Our long-term research objective involves the identification and molecular characterization of the functional segments of the genome associated with specifying the structural, physiological, and behavioral characteristics of the developing mammal. To investigate this problem, we have chosen a genetic approach involving the generation of novel mutations by insertional mutagenesis in transgenic mouse. The mutant genes generated in this manner are tagged with a DNA marker and can be cloned and subjected to an in depth molecular analysis with our available techniques. The mouse is an attractive animal model for these experiments because of its extensive embryologic and genetic history and accessibility to experimental manipulation. With its close evolutionary relationship to humans, we expect that our mouse experiments will facilitate a better understanding of the genes that are associated with both the normal and the abnormal developmental processes in humans. We are proposing to initiate a large scale insertional mutagenesis program here within the Mammalian Genetics Section of the Oak Ridge National Laboratory. We are in a unique position to undertake such a mutagenesis program because of our molecular skills, genetic training and support staff, and facilities which were specifically designed for large scale mouse mutagenesis experiments. Over the course of the next several years, we expect to generate approximately 200 lines of transgenic mice annually and to subject them to a screen for dominant and recessive insertional mutations. In preparation for an in-depth molecular analysis, the mouse genomic sequences flanking the inserted DNA from several mutant animals will be cloned and structurally characterized.